The hypothesis is being tested that phenethylbiguanide and related compounds affect intermediary metabolism of glucose by altering the interaction of divalent metal ions, particularly Ca2ion, with intracellular binding sites. Cationic agents which lower blood sugar are being examined for ability to alter energized flux of Ca2ion into mitochondria as well as Ca2ion efflux. Studies are also planned to attempt affinity labeling of the guanidinium binding site of mitochondria using compounds related to 3,5-dimethylpyrazole-1-carboxamidine.